title: Phenothiazine is a potent inhibitor of prostaglandin E2 production by Candida albicans biofilms.
abstract: Candida albicans is an important opportunistic yeast pathogen of humans and has the ability to form drug-resistant biofilms, with increased expression of multidrug ATP-binding cassette (ABC) transporters. These biofilms are also capable of secreting immune-modulating prostaglandin E2 (PGE2 ) from host-derived arachidonic acid (AA). Phenothiazine, an aromatic amine, and its derivatives display broad activity as inhibitors and antioxidants. These compounds have fungistatic and fungicidal activity against planktonic C. albicans and can inhibit ABC transporters of C. albicans. This study investigated the effect of phenothiazine on biofilm formation, ABC transporters and PGE2 production by C. albicans. This was carried out by growing C. albicans biofilms in the presence of AA and phenothiazine and measuring the biomass as well as reduction of 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5[(phenylamino) carbonyl]-2H tetrazolium hydroxide. The effect on ABC transporters was determined by rhodamine 6G efflux, and the concentration of PGE2 was determined by a monoclonal PGE2 enzyme-linked immunosorbent assay and LC/MS/MS. Our results indicate that phenothiazine can cause a reduction in both the metabolic activity and biomass of C. albicans biofilms, without affecting biofilm morphology or ABC transporters. However, it is a potent inhibitor of PGE2 production by C. albicans biofilms.
authors.affiliation: Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa.
authors.forename: Ruan
authors.initials: R
authors.lastname: Ells
authors.forename: Gabré
authors.initials: G
authors.lastname: Kemp
authors.forename: Jacobus
authors.initials: J
authors.lastname: Albertyn
authors.forename: Johan L F
authors.initials: JL
authors.lastname: Kock
authors.forename: Carolina H
authors.initials: CH
authors.lastname: Pohl
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology*; D012235:Rhodamines / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D010640:Phenothiazines; D012235:Rhodamines; C026188:rhodamine 6G; C031637:phenothiazine; D015232:Dinoprostone
keywords: ABC transporters; antifungal; arachidonic acid; virulence factors